6.2 Somitogenesis and segmentation
4 min read•august 16, 2024
Somitogenesis is a crucial process in early development, forming segmented blocks of mesoderm along the embryo's axis. These somites later differentiate into vertebrae, ribs, and muscles. It's a perfect example of how complex structures arise from simpler precursors.
The molecular clock and explains how somites form at regular intervals. Oscillating gene expression acts as a clock, while signaling gradients create a moving wavefront. This interplay ensures precise timing and positioning of somite boundaries as the embryo grows.
Somitogenesis and Somite Formation
Paraxial Mesoderm and Somite Development
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- Somitogenesis forms paired blocks of mesoderm (somites) along the anterior-posterior axis of the embryo
- located on either side of the neural tube and notochord generates somites
- Somites bud off from the presomitic mesoderm (PSM) in a rostral-to-caudal direction at regular intervals
- PSM divides into more mature anterior region and less differentiated posterior region
- involves epithelialization of mesenchymal cells in anterior PSM creating spherical structure
- Outer epithelial layer surrounds mesenchymal core
- Species-specific somite formation varies in number and timing
- Humans form 42-44 somite pairs over ~4 weeks
Somite Formation Process
- Mesenchymal cells in anterior PSM undergo epithelialization
- Cells reorganize and polarize to form epithelial outer layer
- Extracellular matrix deposition occurs between forming somites
- Somite boundaries established through differential cell adhesion
- Newly formed somites separate from PSM through a "budding off" process
- Each somite develops distinct anterior and posterior compartments
- Somite maturation continues as new somites form caudally
Molecular Clock and Wavefront Model
Clock Component
- Oscillating gene expression in PSM creates temporal periodicity for somite formation
- Key oscillating genes belong to Notch, Wnt, and FGF signaling pathways
- Gene expression cycles match somite formation periodicity
- Hes genes act as transcriptional repressors regulating clock gene oscillations
- Cyclic gene expression propagates as waves through the PSM
- Oscillations synchronized between neighboring cells through cell-cell communication
Wavefront Component
- Moving front of gene expression progresses caudally defining somite competence region
- Opposing gradients establish wavefront:
- FGF/Wnt (high posterior to low anterior)
- Retinoic acid (high anterior to low posterior)
- Gradients create "determination front" where cells become competent to form somites
- FGF and Wnt maintain PSM in undifferentiated state
- Retinoic acid promotes somite differentiation
- Intersection of clock oscillations and wavefront determines somite boundary formation
- Model explains regular interval formation and consistent somite size despite embryonic growth
Notch and Wnt Signaling in Segmentation
Notch Pathway in Molecular Clock
- establishes molecular clock oscillations within PSM
- Cyclic expression of Notch pathway components (receptor, ligands like Delta)
- Notch activation induces Hes gene expression
- Hes proteins repress own transcription creating negative feedback loop
- Oscillations propagate through PSM via synchronized Notch signaling
- Disruption of Notch signaling leads to somite formation defects (irregular boundaries)
Wnt Signaling in Clock and Wavefront
- contributes to both molecular clock and wavefront components
- Maintains undifferentiated state of PSM cells
- Regulates expression of key segmentation genes (T-box transcription factors)
- Wnt signaling gradually declines from posterior to anterior PSM
- Helps establish determination front for somite competence
- Cyclic Wnt target genes (Axin2) contribute to molecular clock mechanism
- Wnt signaling interacts with FGF pathway to regulate PSM maturation
Pathway Interactions
- Cross-talk between Notch, Wnt, and FGF pathways coordinates somite formation
- Notch and Wnt oscillations coupled through shared target genes
- FGF signaling modulates Notch and Wnt activity in PSM
- Retinoic acid antagonizes FGF/Wnt signaling to promote somite differentiation
- Integration of multiple signaling inputs ensures robust segmentation process
- Mutations in pathway components lead to vertebral abnormalities (scoliosis)
Somite Differentiation into Sclerotome, Myotome, and Dermatome
Sclerotome Formation
- forms from ventromedial portion of somite
- Gives rise to vertebrae and ribs
- Induced by signals from notochord and floor plate
- Primary signal: Sonic hedgehog (Shh)
- Shh activates Pax1 expression in sclerotome
- Sclerotome cells undergo epithelial-to-mesenchymal transition
- Migrates around notochord and neural tube to form vertebral bodies
- Sclerotome patterning establishes vertebrae segmentation (resegmentation)
Myotome Development
- Myotome develops from dorsolateral portion of somite
- Gives rise to skeletal muscles of trunk and limbs
- Influenced by signals from dorsal neural tube and surface ectoderm
- Key signals: Wnt proteins and bone morphogenetic proteins (BMPs)
- Myogenic regulatory factors (MRFs) drive muscle cell differentiation
- MyoD, Myf5, myogenin, MRF4
- Myotome cells form early muscle fibers and muscle progenitor cells
- Progenitors migrate to form limb and body wall muscles
Dermatome Specification
- Dermatome forms from dorsal-most region of somite
- Gives rise to dermis of the back
- Regulated by BMP signaling from dorsal neural tube and surface ectoderm
- Dermatome maintains epithelial characteristics longer than other somite regions
- Cells eventually undergo EMT and migrate to form dermis
- Dermatome patterning influenced by positional cues along the body axis
- Contributes to regional specialization of skin (scales, feathers, hair follicles)
Key Terms to Review (18)
Dermatomyotome: The dermatomyotome is a component of the somite that differentiates into two important structures: the dermis, which forms the skin's connective tissue, and the myotome, which gives rise to skeletal muscles. This structure is crucial for proper segmentation and organization during embryonic development, playing a significant role in forming the musculoskeletal system and the dermal layers of the body.
Evolutionary developmental biology: Evolutionary developmental biology, often abbreviated as evo-devo, is a field that explores the relationship between the evolution of organisms and their developmental processes. By examining how changes in developmental pathways can lead to evolutionary changes in form and function, this discipline bridges the gap between genetics, morphology, and evolutionary theory. It helps to understand how specific structures and systems have evolved over time and how variations in these processes can result in the diversity of life forms we see today.
Gene Knockout: Gene knockout is a genetic technique used to inactivate or 'knock out' specific genes in an organism's genome, allowing researchers to study the effects of losing that gene's function. This method is crucial for understanding the roles of particular genes in development, physiology, and disease, especially in areas like cardiovascular development, limb patterning, and body plan organization.
Hox Genes: Hox genes are a group of related genes that play a crucial role in determining the body plan and segment identity of an organism during early development. These genes are responsible for specifying the anterior-posterior axis and influencing the formation of structures in the correct locations along this axis, making them essential for proper embryonic development.
In situ hybridization: In situ hybridization is a technique used to detect specific nucleic acid sequences within fixed tissues or cells, allowing researchers to visualize the spatial expression patterns of genes. This method combines the precision of molecular biology with the structural context of histology, making it vital for understanding developmental processes and gene function during various biological events.
Mesoderm Differentiation: Mesoderm differentiation is the process by which the mesoderm layer of embryonic cells transforms into various specialized cell types and tissues. This process is crucial for forming structures such as muscles, bones, and the cardiovascular system, playing a pivotal role in shaping the developing organism's body plan and organ systems.
Mesp2: Mesp2 is a transcription factor critical for the segmentation process during embryonic development. It plays a vital role in somitogenesis, the formation of somites from the presomitic mesoderm, which is essential for the proper segmentation of the body plan in vertebrates. Mesp2's expression is tightly regulated and marks the future somite boundaries, influencing the development of structures such as vertebrae and muscles.
Notch Signaling: Notch signaling is a fundamental cell communication pathway that regulates cell fate decisions during development and maintains tissue homeostasis. This signaling involves interactions between Notch receptors on one cell and their ligands on adjacent cells, influencing processes such as differentiation, proliferation, and apoptosis.
Paraxial Mesoderm: Paraxial mesoderm is a region of mesoderm located on either side of the notochord during early embryonic development, giving rise to somites, which are segmented blocks of mesoderm. This tissue plays a crucial role in the formation of the axial skeleton, skeletal muscles, and dermis of the skin. The paraxial mesoderm is essential for proper segmentation during somitogenesis, influencing the organization and patterning of developing structures.
Sclerotome: The sclerotome is a part of the somite, specifically the segment of mesoderm that gives rise to the vertebrae and other axial skeleton structures during embryonic development. It plays a crucial role in somitogenesis and segmentation, helping to establish the segmented nature of the vertebrate body plan and contributing to the formation of vertebral bodies and intervertebral discs.
Segment Polarity: Segment polarity refers to the developmental process that establishes the anterior-posterior (head-to-tail) organization within each segment of an organism during early embryogenesis. This is crucial for proper body plan formation as it helps define the boundaries and identity of segments, influencing the differentiation of structures such as limbs and other organs.
Segmental patterning: Segmental patterning refers to the process by which segments or repeated units are formed during embryonic development, especially in the context of body plan organization in multicellular organisms. This concept is crucial for understanding how structures like somites are generated, which contribute to the vertebrate body plan by segmenting the developing embryo into distinct regions, each with specific identities and functions.
Segmentation Clock: The segmentation clock is a molecular mechanism that regulates the periodic formation of somites during embryonic development. It involves a rhythmic expression of specific genes that creates a synchronized pattern of tissue segmentation, which is crucial for the organization of the body plan in vertebrates. This clock-like function ensures that somites are formed in an orderly manner, contributing to the development of the segmented structures of the body, including vertebrae and muscles.
Somite Formation: Somite formation is the process by which paraxial mesoderm segments into somites, which are blocks of mesoderm that develop into structures such as vertebrae, muscles, and dermis. This segmentation is crucial for organizing the body plan during early embryonic development, linking the formation of somites to the establishment of the vertebrate body axis and the subsequent development of the neural tube.
Spatial Organization: Spatial organization refers to the arrangement and distribution of biological structures within a specific area or context, which is crucial for understanding developmental processes and cellular functions. It encompasses how cells, tissues, and organs are positioned relative to one another, influencing their interactions and roles during development and in mature organisms. In developmental biology, this concept is fundamental to processes like somitogenesis, where the organization of somites contributes to the body plan, as well as in techniques like spatial transcriptomics that reveal gene expression patterns in their native context.
Temporal Regulation: Temporal regulation refers to the timing and sequence of developmental events in an organism, ensuring that processes occur at the right time for proper development and function. This concept is crucial in developmental biology as it influences how cells differentiate, tissues form, and organs develop, leading to the organized structure of the organism. Understanding temporal regulation can help explain how certain genes are activated or repressed at specific stages, which is essential for processes like somitogenesis, cell lineage determination, and overall organismal development.
Wavefront model: The wavefront model is a conceptual framework used to describe the spatial and temporal progression of developmental signals during embryogenesis, particularly in the context of somitogenesis. This model helps explain how waves of signaling molecules propagate through the developing tissue, leading to the segmentation and formation of somites in vertebrates.
Wnt Pathway: The Wnt pathway is a complex signaling cascade crucial for various developmental processes, including cell proliferation, differentiation, and fate specification. This pathway plays a pivotal role in somitogenesis, influencing the formation of somites and segmentation, and is also integral to cell differentiation and specialization, directing the fates of progenitor cells. Additionally, it aids in lineage tracing and fate mapping, providing insights into how specific cell types emerge during development.